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Identification of a miRNA multi-targeting therapeutic strategy in glioblastoma

ABSTRACT: Identification of a miRNA multi-targeting therapeutic strategy in glioblastoma

PROVIDER: PRJNA1034152 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26621554.fastq.gz	Fastqsanger.gz
	SRR26621555.fastq.gz	Fastqsanger.gz
	SRR26621556.fastq.gz	Fastqsanger.gz
	SRR26621557.fastq.gz	Fastqsanger.gz
	SRR26621558.fastq.gz	Fastqsanger.gz

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Identification of a miRNA multi-targeting therapeutic strategy in glioblastoma

Project description:Glioblastoma (GBM) is a deadly and the most common primary brain tumor in adults. Due to their regulation of a high number ofmRNA transcripts, microRNAs (miRNAs) are key molecules in the control of biological processes and are thereby promisingtherapeutic targets for GBM patients. In this regard, we recently reported miRNAs as strong modulators of GBM aggressiveness.Here, using an integrative and comprehensive analysis of the TCGA database and the transcriptome of GBM biopsies, we identifiedthree critical and clinically relevant miRNAs for GBM, miR-17-3p, miR-222, and miR-340. In addition, we showed that thecombinatorial modulation of three of these miRNAs efficiently inhibited several biological processes in patient-derived GBM cells ofall these three GBM subtypes (Mesenchymal, Proneural, Classical), induced cell death, and delayed tumor growth in a mouse tumormodel. Finally, in a doxycycline-inducible model, we observed a significant inhibition of GBM stem cell viability and a significantdelay of orthotopic tumor growth. Collectively, our results reveal, for the first time, the potential of miR-17-3p, miR-222 and miR-340multi-targeting as a promising therapeutic strategy for GBM patients.Cell Death and Disease (2023) 14:630 ; https://doi.org/10.1038/s41419-023-06117-z

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Identification of a miRNA multi-targeting therapeutic strategy in glioblastoma.

Project description:Glioblastoma (GBM) is a deadly and the most common primary brain tumor in adults. Due to their regulation of a high number of mRNA transcripts, microRNAs (miRNAs) are key molecules in the control of biological processes and are thereby promising therapeutic targets for GBM patients. In this regard, we recently reported miRNAs as strong modulators of GBM aggressiveness. Here, using an integrative and comprehensive analysis of the TCGA database and the transcriptome of GBM biopsies, we identified three critical and clinically relevant miRNAs for GBM, miR-17-3p, miR-222, and miR-340. In addition, we showed that the combinatorial modulation of three of these miRNAs efficiently inhibited several biological processes in patient-derived GBM cells of all these three GBM subtypes (Mesenchymal, Proneural, Classical), induced cell death, and delayed tumor growth in a mouse tumor model. Finally, in a doxycycline-inducible model, we observed a significant inhibition of GBM stem cell viability and a significant delay of orthotopic tumor growth. Collectively, our results reveal, for the first time, the potential of miR-17-3p, miR-222 and miR-340 multi-targeting as a promising therapeutic strategy for GBM patients.

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